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Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes.

ABSTRACT: Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild-type (WT) mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A more than 20-fold. Upon GH stimulation, 23?827 and 111?939 STAT5A binding sites were detected in WT and STAT5A overexpressing MEFs, respectively. 13?278 and 71?561 peaks contained at least one GAS motif. 1586 and 8613 binding sites were located within 2.5?kb of promoter sequences, respectively. Stringent filtering revealed 78 genes in which the promoter/upstream region (-10?kb to +0.5?kb) was recognized by STAT5 both in WT and STAT5 overexpressing MEFs and 347 genes that bound STAT5 only in overexpressing cells. Genome-wide expression analyses identified that the majority of STAT5-bound genes was not under GH control. Up to 40% of STAT5-bound genes were not expressed. For the first time we demonstrate the magnitude of opportunistic genomic STAT5 binding that does not translate into transcriptional activation of neighboring genes.

SUBMITTER: Zhu BM

PROVIDER: S-EPMC3378893 | biostudies-other | 2012 May

REPOSITORIES: biostudies-other

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Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes.

Zhu Bing-Mei BM Kang Keunsoo K Yu Ji Hoon JH Chen Weiping W Smith Harold E HE Lee Daeyoup D Sun Hong-Wei HW Wei Lai L Hennighausen Lothar L

Nucleic acids research 20120208 10

Signal Transducers and Activators of Transcription (STAT) 5A/B regulate cytokine-inducible genes upon binding to GAS motifs. It is not known what percentage of genes with GAS motifs bind to and are regulated by STAT5. Moreover, it is not clear whether genome-wide STAT5 binding is modulated by its concentration. To clarify these issues we established genome-wide STAT5 binding upon growth hormone (GH) stimulation of wild-type (WT) mouse embryonic fibroblasts (MEFs) and MEFs overexpressing STAT5A m ...[more]

PMID: 22319210

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Project description:Revealing the genetic factors underlying yield and agronomic traits in wheat are an imperative need for covering the global food demand. Yield boosting requires a deep understanding of the genetic basis of grain yield-related traits (e.g., spikelet fertility and sterility). Here, we have detected much natural variation among ancient hexaploid wheat accessions in twenty-two agronomic traits collected over eight years of field experiments. A genome-wide association study (GWAS) using 15?K single nucleotide polymorphisms (SNPs) was applied to detect the genetic basis of studied traits. Subsequently, the GWAS output was reinforced via other statistical and bioinformatics analyses to detect putative candidate genes. Applying the genome-wide SNP-phenotype network defined the most decisive SNPs underlying the traits. Six pivotal SNPs, co-located physically within the genes encoding enzymes, hormone response, metal ion transport, and response to oxidative stress have been identified. Of these, metal ion transport and Gibberellin 2-oxidases (GA2oxs) genes showed strong involvement in controlling the spikelet sterility, which had not been reported previously in wheat. SNP-gene haplotype analysis confirmed that these SNPs influence spikelet sterility, especially the SNP co-located on the exon of the GA2ox gene. Interestingly, these genes were highly expressed in the grain and spike, demonstrating their pivotal role in controlling the trait. The integrative analysis strategy applied in this study, including GWAS, SNP-phenotype network, SNP-gene haplotype, expression analysis, and genome-wide prediction (GP), empower the identification of functional SNPs and causal genes. GP outputs obtained in this study are encouraging for the implementation of the traits to accelerate yield improvement by making an early prediction of complex yield-related traits in wheat. Our findings demonstrate the usefulness of the ancient wheat material as a valuable resource for yield-boosting. This is the first comprehensive genome-wide analysis for spikelet sterility in wheat, and the results provide insights into yield improvement.

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Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes.

Publications

Genome-wide analyses reveal the extent of opportunistic STAT5 binding that does not yield transcriptional activation of neighboring genes.

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